反应详情

温度

100 °C

7-Bromo-5-fluoro-quinazolin-2-amine (8.02 g, 33.1 mmol, 1.00 equiv), Pd(OAc)2 (750 mg, 3.34 mmol, 0.10 equiv), 1,3-bis(dicyclohexylphosphino)propane bis(tetrafluoroborate) (2.04 g, 3.22 mmol, 0.10 equiv) and K2CO3 (9.27 g, 66.4 mmol, 2.00 equiv) were suspended together in DMF (100 ml) under nitrogen and treated with anhydrous MeOH (13.5 mL, 333 mmol, 10 equiv). The flask was thoroughly flushed with carbon monoxide, and then heated to 100° C. with a continuous flow of carbon monoxide, which was switched to a static positive pressure on reaching temperature. After 6 h the reaction was cooled. The mixture was diluted with water (200 mL) and extracted twice into EtOAc. The combined organic phases were washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo to afford a crude orange solid (6.76 g) which was absorbed onto SiO2 and purified by automated SiO2 chromatography eluting with an EtOAc/heptane gradient (0 to 100% EtOAc) to afford 4.30 g (59%) of methyl 2-amino-5-fluoroquinazoline-7-carboxylate as a pale orange solid: 1H NMR (400 MHz, CDCl3) δ 9.35 (s, 1H), 8.07 (s, 1H), 7.48 (dd, J=10.0, 1.0 Hz, 1H), 5.35 (br s, 2H), 3.98 (s, 3H); LCMS: MH+222.2

1. customThe flask was thoroughly flushed with carbon monoxide
2. temperatureAfter 6 h the reaction was cooled
3. additionThe mixture was diluted with water (200 mL)
4. extractionextracted twice into EtOAc
5. washThe combined organic phases were washed with water and brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto afford a crude orange solid (6.76 g) which
10. customwas absorbed onto SiO2
11. custompurified by automated SiO2 chromatography
12. washeluting with an EtOAc/heptane gradient (0 to 100% EtOAc)